Increased variability, or “dispersion,” of myocardial electrical activation and recovery times over the geography of the heart during a cardiac cycle is known to increase the propensity for cardiac arrhythmias. Times of activation, observed as the QRS signal on an ECG, and recovery, observed as the T-wave, can be measured on a multiple-lead surface ECG. Prolonged Q-T interval and interlead variability of the Q-T interval are strong predictors of cardiac arrhythmias. Repolarization dispersion as well as the orientation of repolarization gradients may be important determinants of the vulnerability to re-entrant tachycardias as previously reported several years ago in prior publications. Heart failure patients having greater dispersion of the QRS and the Q-T interval are reportedly at a greater risk for sudden cardiac death and have a lower chance of survival.
Non-invasive surface ECG studies can be performed for measuring QT interval dispersion. The difference and variance of the difference between a minimum and maximum Q-T interval measured using standard 12-lead ECG provide an index of dispersion. A long Q-T interval is a reflection of myocyte action potential prolongation. Action potential prolongation associated with heart failure, congenital long Q-T syndrome, and drug-induced effects is reportedly linked to increased dispersion of the activation-recovery interval (ARI) over the heart. The ARI can be defined as the interval between a point selected on the QRS wave to represent the activation time and a point selected on the T-wave to represent the recovery time on an ECG or cardiac electrogram (EGM) signal. Prolonged ARI and increased dispersion of activation, recovery and/or ARI create an important substrate for arrhythmias.
Thus, measurement of the dispersion of activation and recovery times and the ARI is of interest for a number of diagnostic and prognostic applications. A method and apparatus for non-invasive dynamic tracking and diagnosing of cardiac vulnerability to ventricular fibrillation using leads placed on the surface of the chest for simultaneous assessment of T-wave alternans, Q-T interval dispersion, and heart rate variability are generally disclosed in U.S. Pat. No. 5,560,370 issued to Verrier et al. A method and apparatus for analyzing QT dispersion in ECG lead signals is generally disclosed in U.S. Pat. No. 5,792,065, issued to Xue et al., in which T-wave markers are determined automatically for making Q-T dispersion measurements from ECG signals. However, it is desirable to provide chronic ambulatory, monitoring of electrical dispersion in heart failure patients or in patients having other conditions known to cause a propensity for arrhythmias such that a worsening of the patient's disease status or arrhythmia risk may be quickly diagnosed and treated.
Methods for chronically measuring action potential duration are generally disclosed in U.S. Pat. No. 6,152,882 issued to Prutchi and in U.S. Pat. No. 6,522,904 issued to Mika. A cardioelectric apparatus for the early detection of a tachycardia is generally disclosed in U.S. Pat. No. 6,466,819 issued to Weiss wherein time-variant measurements of paired heart rate and action potential duration measurements are compared for determining a tachycardia risk. Geographic dispersion of action potential duration at a point in time is not disclosed. An implantable cardiac stimulation device that monitors progression or regression of a patient's heart condition by determining ventricular repolarization interval dispersions spaced apart over time is generally disclosed in U.S. Pat. No. 6,456,880 issued to Park et al. The ventricular repolarization interval dispersions are determined based upon the difference between a maximum ventricular repolarization interval measured with one of a plurality of electrode configurations and a minimum ventricular repolarization interval measured with another one of the plurality of electrode configurations. The plurality of electrode configurations selected include electrodes positioned in both the right and left side of the heart to preclude localized sensing.
However, localized measurement of activation and recovery times at two or more sites for determining electrical dispersion provide more accurate and site-specific information compared to measurements made from relatively global signals. Determination of the ARI from a unipolar EGM signal is closely correlated to the duration of the local monophasic action potential. Furthermore, differences between localized measurements of activation and recovery times made at two or more sites during the same cardiac cycle provide an accurate measurement of the geographic dispersion of activation and recovery and the orientation of the dispersion.
Chronic, ambulatory monitoring of the heterogeneity of activation and refractoriness could also be useful in managing the delivery of a number of cardiac therapies. Cardiac resynchronization therapy (CRT) has been clinically demonstrated to improve indices of cardiac function in patients suffering from congestive heart failure. Cardiac pacing may be applied to one or both ventricles or multiple heart chambers, including one or both atria, to improve cardiac chamber coordination, which in turn improves stroke volume and pumping efficiency. Clinical follow-up of patients undergoing resynchronization therapy has shown improvements in hemodynamic measures of cardiac function, left ventricular volumes, and wall motion. However, not all patients respond favorably to cardiac resynchronization therapy. Physicians are challenged in selecting patients that will benefit and in selecting the optimal pacing intervals applied between the atria and ventricles (A-V intervals) and between the left and right ventricles (V-V intervals) to resynchronize the heart chamber contractions.
Selection of pacing intervals may be based on echocardiographic studies performed acutely to determine the settings resulting in the best hemodynamic response. It can be reasonably assumed that improved mechanical coordination gained from CRT therapy is associated with reduced dispersion of electrical activity as well. Therefore a method for optimizing CRT pacing intervals based on reducing electrical dispersion of activation, recovery, or the interval between activation and recovery (ARI) is desirable.
From the above discussion, it is apparent that a need remains for a method and associated apparatus for monitoring dispersion of electrical activation and recovery based on local or global cardiac signals or both. Assessment of electrical dispersion is useful in monitoring heart failure status and arrhythmia risk. Analysis of activation and recovery time and ARI dispersion would also be useful in controlling the delivery of anti-arrhythmic drugs or other pharmaceutical agents or other types of therapies, such as spinal cord stimulation, that affect the electrical activity of the heart or have autonomic influences on the heart. It is further desirable to provide a method for controlling the timing of cardiac resynchronization therapy so as to increase the homogeneity of electrical activation and recovery.